This invention relates to a method and apparatus for detecting changes in voltage potential developed in a medium. More particularly, this invention pertains to a method and apparatus for detecting metabolic activity in a growth medium based upon changes of electrical characteristics, such as the impedance, of that medium.
As a means of making rapid and accurate measurements of various media to determine whether metabolic activity is occurring, and sometimes identifying and enumerating the particular microorganisms involved, it has become known to correlate changes of electrical impedance with such activity. By establishing a relationship between metabolic activity and change of an electrical characteristic, such as impedance, of the growth medium, tremendous savings in time to detect bacteria presence or other microorganism and/or cellular activity have been achieved along with greater accuracy and more reliable test results than in the known turbidity analysis tests or radiometric methods. Well conceived equipment such as described in U.S. Pat. No. 3,984,766 to Thornton now makes it possible to automatically measure impedance ratios of a pair of cells containing a selected medium, one medium of which contains a suspected microorganism contaminant. The changes of impedance ratios of the media are directly related to growth of a microorganism therein. By using a ratio of impedance it is possible to eliminate all the variables affecting impedance changes except organism growth; these influential variables include temperature fluctuations, gradual corrosion of electrodes, aging of the medium, medium changes due to absorption of gases, etc. Moreover, the Thornton equipment is capable of handling the testing of many samples rapidly, accurately and automatically.
Other devices have been described, for instance, by Ur in British Specification No. 1,299,363 and U.S. Pat. No. 3,699,437, but such devices neither have the capacity nor the automation and rapidity of measurement as does the Thornton equipment.
As this technique of measuring reactions of an electrical characteristic of a medium to indicate metabolic activity occurring therein becomes more acceptable to users and potential users, additional improvements in these type devices are being sought. These sought-after improvements include the capability to test hundreds, even thousands, of samples in one system while keeping space constraints under consideration; greater accuracy in characterizing not only the presence of microorganisms growing in a medium, but their identification, levels of concentration and susceptibility to antibiotics; the ability to lower the threshold at which to detect the presence of microorganisms; and a computer system to monitor a very large number of test samples to analyze various data inputs from each and provide the user with a variety of results including specific identification of microorganisms in the shortest time span.
One of the shortcomings of the Thornton system as described in U.S. Pat. No. 3,984,766, and other impedance measuring systems related to microorganism growth, is in the lack of ability to handle very large numbers of samples during one test. While it is explained in the Thornton patent that large numbers of cell pairs can be measured in that apparatus, a number of factors combine to realistically limit the actual number of cell samples which can be measured during one test: the electrical circuit, in which the source of electrical energy, the oscillator, is a constant voltage source across which each pair of cells is serially connected; the fact that each sample or specimen cell has a reference cell physically proximate thereto and electrically connected in the circuit; and as a number of pairs of cells accumulate, their physical presence removes them further from the source of electrical energy. In practice, the oscillator provides a given voltage to all of the pairs of cells in parallel with each other. It can be appreciated that with a fixed voltage souuce there will be differences of voltage "seen" across each cell pair, especially at the cells which are furthest in distance from the voltage source or as cells are added to be tested in the fixed voltage system. Consequently, true voltage readings are not attained across the cell pairs at increased distance from the source since the lengths of electrical leads provides a transmission loading effect. Proper voltage requirements are critical in this type of system because extremely small voltage changes in the cells are the indicative means of pinpointing microorganism growth. Clearly, with this type system accuracy and reliability of measurements are sacrificed when the number of samples in the system are sufficient to produce variations in or unequal voltages applied across those samples. Of course, closely packaged samples can reduce the effect of transmission loading, but at some point the space physically occupied by a large number of samples will produce a line length loading problem.
Moreover, it must be kept in mind that the Thornton system has a reference cell for every sample cell. Thus, double the space and electrical wiring is needed for every additional sample to be tested. While this system provides excellent results for a moderately large number of test samples, there is indeed room for improvement in many aspects of such a system in order to accommodate a very large number of samples, such as in the hundreds, to be monitored during a single test.